Cell isolation device and method

Abstract

The present invention relates to a device and method for automatically isolating viable cells from connective, epithelial or other tissue, and, if the tissue is multilayered, for automatically separating one tissue layer from another.

The invention claimed is: 
     
         1 . An automatically operable cell isolation device, comprising:
 a) a liquid distribution unit that includes a plurality of separate liquid containers;   b) a biopsy kit by which a sample of tissue is extractable;   c) a main disposable unit configured to cooperate with one or more process containers and with a valve array;   d) one or more final product bags for receiving isolated cells,
 wherein a first portion of said valve array interfaces between said biopsy kit and one of said process containers, a second portion of said valve array interfaces between said liquid distribution unit and said one or more process containers, and a third portion of said valve array interfaces between said one or more process containers and said one or more final product bags, wherein said valve array is configurable to effect a desired cell isolation procedure; 
   e) comprising a valve controller for facilitating selective actuation of each valve of the valve array to achieve a desired valve configuration;   f) means for generating fluid flow and tissue transfer between the biopsy kit and the one or more process containers or between the one or more process containers and the one or more final product bags in conjunction with the desired valve configuration; and   g) a sequencer module in data communication with the valve controller and the fluid generating means for facilitating selective actuation of each valve of the valve array and of the fluid generating means in each step of a sequence of the desired cell isolation procedure.   
     
     
         2 . The cell isolation device according to  claim 1 , further comprising a software module in data communication with the sequencer module for generating a user interface by which one of a plurality of cell isolation procedure sequences are selectable. 
     
     
         3 . The cell isolation device according to  claim 1 , wherein one of the liquid containers is prefilled with a washing solution, the cell isolation device being operable to flush tissue debris remaining in the biopsy kit, the one or more process containers, or each of the tubes with the washing solution. 
     
     
         4 . The cell isolation device according to  claim 1 , wherein at least one of the liquid containers is prefilled with an isolation agent or with a separation agent. 
     
     
         5 . The cell isolation device according to  claim 1 , further comprising a shaker device that is kinematically connected with a corresponding one of the one or more process containers. 
     
     
         6 . The cell isolation device according to  claim 5 , wherein the shaker device comprises a holder by which the corresponding process container is held, a rod about which said holder is pivotable, an appendage protruding from said holder, and means for applying a driving force to said appendage that causes said holder to rotate in a similar direction about said rod and to shake liquid contained within the corresponding process container. 
     
     
         7 . The cell isolation device according to  claim 6 , wherein the rod is substantially horizontally disposed and is connected to resilient means that induces precessional motion during pivoting displacement of the holder. 
     
     
         8 . The cell isolation device according to  claim 6 , wherein the means for applying a driving force comprises eccentric rotatably driven means protruding through an aperture formed in the appendage, wherein said driven means is configured to forcibly contact a wall of the aperture and to apply the driving force to the appendage. 
     
     
         9 . The cell isolation device according to  claim 5 , further comprising a shaker controller in data communication with both of the shaker device and the sequencer module to facilitate selective operation of the shaker device and to facilitate performance of the desired cell isolation procedure. 
     
     
         10 . The cell isolation device according to  claim 1 , wherein at least one of the liquid containers is an enzyme container; the cell isolation device further comprises at least one climate control chamber within which a corresponding enzyme container is retained throughout the cell isolation procedure; and each of said at least one climate control chambers comprises a Peltier unit for selective temperature control within a climate control chamber interior. 
     
     
         11 . The cell isolation device according to  claim 5 , wherein the shaker device further comprises a contact heater for heating the process container. 
     
     
         12 . An automatically operable cell isolation device, comprising:
 a) a liquid distribution unit that includes a plurality of separate liquid containers;   b) a biopsy kit by which a sample of tissue is extractable;   c) a main disposable unit configured to cooperate with one or more process containers and with a valve array;   d) one or more final product bags for receiving isolated cells,
 wherein a first portion of said valve array interfaces between said biopsy kit and one of said process containers, a second portion of said valve array interfaces between said liquid distribution unit and said one or more process containers, and a third portion of said valve array interfaces between said one or more process containers and said one or more final product bags, wherein said valve array is configurable to effect a desired cell isolation procedure; 
 wherein the main disposable unit comprises a disposable tube system for being in fluid communication with each of the first, second and third portions of the valve array through which liquid discharged from the liquid distribution unit is selectively flowable; and 
   e) a housing in which are mounted a plurality of electrical or electronic components including the valve array which are configured to effect the desired cell isolation procedure;
 wherein the main disposable unit is a carrier in which the tube system is encapsulated and which is adapted to be securely coupled in error-free fashion with a front panel of the housing such that the tube system is set in fluid communication with each of the first, second and third portions of the valve array. 
   
     
     
         13 . The cell isolation device according to  claim 12 , wherein the main disposable unit comprises a plurality of aseptic connectors, to each corresponding aseptic connector one of the biopsy kit and the liquid containers is connectable. 
     
     
         14 . The cell isolation device according to  claim 12 , wherein the plurality of liquid containers, the one or more process containers, the one or more final product bags, and each tube of the tube system are made of a sterile and biocompatible material. 
     
     
         15 . The cell isolation device according to  claim 12 , wherein the valve array is an array of pinch valves each of which configured with a pinch valve assembly that protrudes forwardly from the housing front panel. 
     
     
         16 . The cell isolation device according to  claim 15 , wherein the pinch valve assembly comprises an abutment and an eccentrically rotating pin to define therebetween an interspace within which a tube of the tube system is restrictedly insertable and pinchable, the tube being insertable simultaneously within the interspace of a plurality of adjacent pinch valve assemblies. 
     
     
         17 . The cell isolation device according to  claim 16 , wherein the pinch valve assembly is self-lockable upon contact between a radial protruding portion and a hard-stop portion when the pin has eccentrically rotated beyond a dead center line. 
     
     
         18 . The cell isolation device according to  claim 12 , wherein the tube system is closed to facilitate aseptic operation of the cell isolation device in a non-sterile environment without risk of contamination. 
     
     
         19 . The cell isolation device according to  claim 14 , wherein the process container comprises a bottom strainer for straining skin pieces during a washing operation or debris during harvesting of isolated cells. 
     
     
         20 . A method for automatically performing a cell isolation procedure, comprising the steps of:
 a) providing a housing in which are mounted a plurality of electrical or electronic components configured to effect a desired cell isolation procedure;   b) securely coupling a carrier, in which a tube system through which one or more isolation agents for isolating extracted tissue is flowable is encapsulated, with the housing, such that the tube system is selectively set in communication by error-free fashion with the plurality of electrical or electronic components after the carrier is coupled with the housing;   c) introducing a tissue sample into a tube of the tube system;   d) selecting a desired protocol for performing a cell isolation procedure by means of one of the electronic components; and   e) performing the cell isolation procedure by sequentially operating the plurality of electrical or electronic components until the one or more isolation agents flows through the tube system and sufficiently acts on the introduced extracted tissue to isolate a cell population residing in the introduced extracted tissue to a single cell level.   
     
     
         21 . The method according to  claim 20 , wherein the one or more isolation agents flows through the tube system which is closed to facilitate aseptic operation of a cell isolation device in a non-sterile environment without risk of contamination.